SummaryDespite considerable advances in drug discovery, resistance to anticancer chemotherapy confounds the effective treatment of patients. Cancer cells can acquire broad cross-resistance to mechanistically and structurally unrelated drugs. P-glycoprotein (Pgp) actively extrudes many types of drugs from cancer cells, thereby conferring resistance to those agents. The central tenet of my work is that Pgp, a universally accepted biomarker of drug resistance, should in addition be considered as a molecular target of multidrug-resistant (MDR) cancer cells. Successful targeting of MDR cells would reduce the tumor burden and would also enable the elimination of ABC transporter-overexpressing cancer stem cells that are responsible for the replenishment of tumors. The proposed project is based on the following observations:
- First, by using a pharmacogenomic approach, I have revealed the hidden vulnerability of MDRcells (Szakács et al. 2004, Cancer Cell 6, 129-37);
- Second, I have identified a series of MDR-selective compounds with increased toxicity toPgp-expressing cells
(Turk et al.,Cancer Res, 2009. 69(21));
- Third, I have shown that MDR-selective compounds can be used to prevent theemergence of MDR (Ludwig, Szakács et al. 2006, Cancer Res 66, 4808-15);
- Fourth, we have generated initial pharmacophore models for cytotoxicity and MDR-selectivity (Hall et al. 2009, J Med Chem 52, 3191-3204).
I propose a comprehensive series of studies that will address thefollowing critical questions:
- First, what is the scope of MDR-selective compounds?
- Second, what is their mechanism of action?
- Third, what is the optimal therapeutic modality?
Extensive biological, pharmacological and bioinformatic analyses will be utilized to address four major specific aims. These aims address basic questions concerning the physiology of MDR ABC transporters in determining the mechanism of action of MDR-selective compounds, setting the stage for a fresh therapeutic approach that may eventually translate into improved patient care.

Despite considerable advances in drug discovery, resistance to anticancer chemotherapy confounds the effective treatment of patients. Cancer cells can acquire broad cross-resistance to mechanistically and structurally unrelated drugs. P-glycoprotein (Pgp) actively extrudes many types of drugs from cancer cells, thereby conferring resistance to those agents. The central tenet of my work is that Pgp, a universally accepted biomarker of drug resistance, should in addition be considered as a molecular target of multidrug-resistant (MDR) cancer cells. Successful targeting of MDR cells would reduce the tumor burden and would also enable the elimination of ABC transporter-overexpressing cancer stem cells that are responsible for the replenishment of tumors. The proposed project is based on the following observations:
- First, by using a pharmacogenomic approach, I have revealed the hidden vulnerability of MDRcells (Szakács et al. 2004, Cancer Cell 6, 129-37);
- Second, I have identified a series of MDR-selective compounds with increased toxicity toPgp-expressing cells
(Turk et al.,Cancer Res, 2009. 69(21));
- Third, I have shown that MDR-selective compounds can be used to prevent theemergence of MDR (Ludwig, Szakács et al. 2006, Cancer Res 66, 4808-15);
- Fourth, we have generated initial pharmacophore models for cytotoxicity and MDR-selectivity (Hall et al. 2009, J Med Chem 52, 3191-3204).
I propose a comprehensive series of studies that will address thefollowing critical questions:
- First, what is the scope of MDR-selective compounds?
- Second, what is their mechanism of action?
- Third, what is the optimal therapeutic modality?
Extensive biological, pharmacological and bioinformatic analyses will be utilized to address four major specific aims. These aims address basic questions concerning the physiology of MDR ABC transporters in determining the mechanism of action of MDR-selective compounds, setting the stage for a fresh therapeutic approach that may eventually translate into improved patient care.

SummaryWireless power transfer (WPT), pioneered by Tesla, is an idea at least as old as radio communications. However, on the one hand, due to health concerns and the large antenna dimensions required for transmission of high energy levels, until recently WPT has been limited mostly to very short distance applications. On the other hand, recent advances in silicon technology have significantly reduced the energy needs of electronic systems, making WPT over radio waves a potential source of energy for low power devices. Although WPT through radio waves has already found various short-range applications (such as the radio-frequency identification technology, healthcare monitoring etc.), its integration as a building block in the operation of wireless communications systems is still unexploited. On the other hand, conventional radio wave based information and energy transmissions have largely been designed separately. However, many applications can benefit from simultaneous wireless information and power transfer (SWIPT).
The overall objective of the APOLLO project is to study the integration of WPT/SWIPT technology into future wireless communication systems. Compared to past and current research efforts in this area, our technical approach is deeply interdisciplinary and more comprehensive, combining the expertise of wireless communications, control theory, information theory, optimization, and electronics/microwave engineering.
The key outcomes of the project include: 1) a rigorous and complete mathematical theory for WPT/SWIPT via information/communication/control theoretic studies; 2) new physical and cross-layer mechanisms that will enable the integration of WPT/SWIPT into future communication systems; 3) new network architectures that will fully exploit potential benefits of WPT/SWIPT; and 4) development of a proof-of-concept by implementing highly-efficient and multi-band metamaterial energy harvesting sensors for SWIPT.

Wireless power transfer (WPT), pioneered by Tesla, is an idea at least as old as radio communications. However, on the one hand, due to health concerns and the large antenna dimensions required for transmission of high energy levels, until recently WPT has been limited mostly to very short distance applications. On the other hand, recent advances in silicon technology have significantly reduced the energy needs of electronic systems, making WPT over radio waves a potential source of energy for low power devices. Although WPT through radio waves has already found various short-range applications (such as the radio-frequency identification technology, healthcare monitoring etc.), its integration as a building block in the operation of wireless communications systems is still unexploited. On the other hand, conventional radio wave based information and energy transmissions have largely been designed separately. However, many applications can benefit from simultaneous wireless information and power transfer (SWIPT).
The overall objective of the APOLLO project is to study the integration of WPT/SWIPT technology into future wireless communication systems. Compared to past and current research efforts in this area, our technical approach is deeply interdisciplinary and more comprehensive, combining the expertise of wireless communications, control theory, information theory, optimization, and electronics/microwave engineering.
The key outcomes of the project include: 1) a rigorous and complete mathematical theory for WPT/SWIPT via information/communication/control theoretic studies; 2) new physical and cross-layer mechanisms that will enable the integration of WPT/SWIPT into future communication systems; 3) new network architectures that will fully exploit potential benefits of WPT/SWIPT; and 4) development of a proof-of-concept by implementing highly-efficient and multi-band metamaterial energy harvesting sensors for SWIPT.

Host Institution (HI)BIOSENSE INSTITUTE - RESEARCH AND DEVELOPMENT INSTITUTE FOR INFORMATION TECHNOLOGIES IN BIOSYSTEMS

Call DetailsStarting Grant (StG), SH6, ERC-2014-STG

SummaryThe BIRTH project will investigate the key biological and cultural mechanisms affecting fertility rates resulting the Neolithic Demogaphic Transition, the major demographic shift in human evolution. We integrate skeletal markers with micro-nutritional and macro-scaled cultural effects on fertility rates during the Early-Middle Holocene (10000-5000 BC) in the Central Balkans. Human, animal and plant remains, will be analysed using methods from bioarchaeological, forensic, chemical sciences in order to: 1) Investigate variability in the pattern of birth rates (number of pregnancies, interval(s) between them and the duration of the reproductive period) through histological analysis of irregularities in tooth cementum of women; 2) Determine paleoobstetric and neonatal body characteristics, health status and nutrition through analysis of skeletal remains; 3) Determine micronutritional changes during the Early-Middle Holocene through trace element (Zn, Ca and Fe) analysis; 4) Investigate the micro and macronutritional value of prehistoric foodstuffs, through an analysis of animal and plant remains and to compare the nutritional intake in relation to health and fertility; 5) Establish a chronology of the NDT in the Balkans by summed radiocarbon probability distributions; 6) Explore the possible role of culture in driving fertility increases, through analysis of community attitudes to birthing trough investigation of neonate graves and artifact connected to the birthing process. Given that the issues of health and fertility are of utmost importance in the present as they were in the past, the BIRTH project offers new understanding of biocultural mechanisms which led to fertility increase and novel approaches to ancient skeletal heritage, and emphasizes their great potential for modern humanity.

The BIRTH project will investigate the key biological and cultural mechanisms affecting fertility rates resulting the Neolithic Demogaphic Transition, the major demographic shift in human evolution. We integrate skeletal markers with micro-nutritional and macro-scaled cultural effects on fertility rates during the Early-Middle Holocene (10000-5000 BC) in the Central Balkans. Human, animal and plant remains, will be analysed using methods from bioarchaeological, forensic, chemical sciences in order to: 1) Investigate variability in the pattern of birth rates (number of pregnancies, interval(s) between them and the duration of the reproductive period) through histological analysis of irregularities in tooth cementum of women; 2) Determine paleoobstetric and neonatal body characteristics, health status and nutrition through analysis of skeletal remains; 3) Determine micronutritional changes during the Early-Middle Holocene through trace element (Zn, Ca and Fe) analysis; 4) Investigate the micro and macronutritional value of prehistoric foodstuffs, through an analysis of animal and plant remains and to compare the nutritional intake in relation to health and fertility; 5) Establish a chronology of the NDT in the Balkans by summed radiocarbon probability distributions; 6) Explore the possible role of culture in driving fertility increases, through analysis of community attitudes to birthing trough investigation of neonate graves and artifact connected to the birthing process. Given that the issues of health and fertility are of utmost importance in the present as they were in the past, the BIRTH project offers new understanding of biocultural mechanisms which led to fertility increase and novel approaches to ancient skeletal heritage, and emphasizes their great potential for modern humanity.

Max ERC Funding

1 714 880 €

Duration

Start date: 2015-10-01, End date: 2020-09-30

Project acronymBRAINCANNABINOIDS

ProjectUnderstanding the molecular blueprint and functional complexity of the endocannabinoid metabolome in the brain

SummaryWe and others have recently delineated the molecular architecture of a new feedback pathway in brain synapses, which operates as a synaptic circuit breaker. This pathway is supposed to use a group of lipid messengers as retrograde synaptic signals, the so-called endocannabinoids. Although heterogeneous in their chemical structures, these molecules along with the psychoactive compound in cannabis are thought to target the same effector in the brain, the CB1 receptor. However, the molecular catalog of these bioactive lipids and their metabolic enzymes has been expanding rapidly by recent advances in lipidomics and proteomics raising the possibility that these lipids may also serve novel, yet unidentified physiological functions. Thus, the overall aim of our research program is to define the molecular and anatomical organization of these endocannabinoid-mediated pathways and to determine their functional significance. In the present proposal, we will focus on understanding how these novel pathways regulate synaptic and extrasynaptic signaling in hippocampal neurons. Using combination of lipidomic, genetic and high-resolution anatomical approaches, we will identify distinct chemical species of endocannabinoids and will show how their metabolic enzymes are segregated into different subcellular compartments in cell type- and synapse-specific manner. Subsequently, we will use genetically encoded gain-of-function, loss-of-function and reporter constructs in imaging experiments and electrophysiological recordings to gain insights into the diverse tasks that these new pathways serve in synaptic transmission and extrasynaptic signal processing. Our proposed experiments will reveal fundamental principles of intercellular and intracellular endocannabinoid signaling in the brain.

We and others have recently delineated the molecular architecture of a new feedback pathway in brain synapses, which operates as a synaptic circuit breaker. This pathway is supposed to use a group of lipid messengers as retrograde synaptic signals, the so-called endocannabinoids. Although heterogeneous in their chemical structures, these molecules along with the psychoactive compound in cannabis are thought to target the same effector in the brain, the CB1 receptor. However, the molecular catalog of these bioactive lipids and their metabolic enzymes has been expanding rapidly by recent advances in lipidomics and proteomics raising the possibility that these lipids may also serve novel, yet unidentified physiological functions. Thus, the overall aim of our research program is to define the molecular and anatomical organization of these endocannabinoid-mediated pathways and to determine their functional significance. In the present proposal, we will focus on understanding how these novel pathways regulate synaptic and extrasynaptic signaling in hippocampal neurons. Using combination of lipidomic, genetic and high-resolution anatomical approaches, we will identify distinct chemical species of endocannabinoids and will show how their metabolic enzymes are segregated into different subcellular compartments in cell type- and synapse-specific manner. Subsequently, we will use genetically encoded gain-of-function, loss-of-function and reporter constructs in imaging experiments and electrophysiological recordings to gain insights into the diverse tasks that these new pathways serve in synaptic transmission and extrasynaptic signal processing. Our proposed experiments will reveal fundamental principles of intercellular and intracellular endocannabinoid signaling in the brain.

Max ERC Funding

1 638 000 €

Duration

Start date: 2009-11-01, End date: 2014-10-31

Project acronymCABUM

ProjectAn investigation of the mechanisms at the interaction between cavitation bubbles and contaminants

Researcher (PI)Matevz DULAR

Host Institution (HI)UNIVERZA V LJUBLJANI

Call DetailsConsolidator Grant (CoG), PE8, ERC-2017-COG

SummaryA sudden decrease in pressure triggers the formation of vapour and gas bubbles inside a liquid medium (also called cavitation). This leads to many (key) engineering problems: material loss, noise and vibration of hydraulic machinery. On the other hand, cavitation is a potentially a useful phenomenon: the extreme conditions are increasingly used for a wide variety of applications such as surface cleaning, enhanced chemistry, and waste water treatment (bacteria eradication and virus inactivation).
Despite this significant progress a large gap persists between the understanding of the mechanisms that contribute to the effects of cavitation and its application. Although engineers are already commercializing devices that employ cavitation, we are still not able to answer the fundamental question: What precisely are the mechanisms how bubbles can clean, disinfect, kill bacteria and enhance chemical activity? The overall objective of the project is to understand and determine the fundamental physics of the interaction of cavitation bubbles with different contaminants. To address this issue, the CABUM project will investigate the physical background of cavitation from physical, biological and engineering perspective on three complexity scales: i) on single bubble level, ii) on organised and iii) on random bubble clusters, producing a progressive multidisciplinary synergetic effect.
The proposed synergetic approach builds on the PI's preliminary research and employs novel experimental and numerical methodologies, some of which have been developed by the PI and his research group, to explore the physics of cavitation behaviour in interaction with bacteria and viruses.
Understanding the fundamental physical background of cavitation in interaction with contaminants will have a ground-breaking implications in various scientific fields (engineering, chemistry and biology) and will, in the future, enable the exploitation of cavitation in water and soil treatment processes.

A sudden decrease in pressure triggers the formation of vapour and gas bubbles inside a liquid medium (also called cavitation). This leads to many (key) engineering problems: material loss, noise and vibration of hydraulic machinery. On the other hand, cavitation is a potentially a useful phenomenon: the extreme conditions are increasingly used for a wide variety of applications such as surface cleaning, enhanced chemistry, and waste water treatment (bacteria eradication and virus inactivation).
Despite this significant progress a large gap persists between the understanding of the mechanisms that contribute to the effects of cavitation and its application. Although engineers are already commercializing devices that employ cavitation, we are still not able to answer the fundamental question: What precisely are the mechanisms how bubbles can clean, disinfect, kill bacteria and enhance chemical activity? The overall objective of the project is to understand and determine the fundamental physics of the interaction of cavitation bubbles with different contaminants. To address this issue, the CABUM project will investigate the physical background of cavitation from physical, biological and engineering perspective on three complexity scales: i) on single bubble level, ii) on organised and iii) on random bubble clusters, producing a progressive multidisciplinary synergetic effect.
The proposed synergetic approach builds on the PI's preliminary research and employs novel experimental and numerical methodologies, some of which have been developed by the PI and his research group, to explore the physics of cavitation behaviour in interaction with bacteria and viruses.
Understanding the fundamental physical background of cavitation in interaction with contaminants will have a ground-breaking implications in various scientific fields (engineering, chemistry and biology) and will, in the future, enable the exploitation of cavitation in water and soil treatment processes.

Max ERC Funding

1 904 565 €

Duration

Start date: 2018-07-01, End date: 2023-06-30

Project acronymCholAminCo

ProjectSynergy and antagonism of cholinergic and dopaminergic systems in associative learning

SummaryNeuromodulators such as acetylcholine and dopamine are able to rapidly reprogram neuronal information processing and dynamically change brain states. Degeneration or dysfunction of cholinergic and dopaminergic neurons can lead to neuropsychiatric conditions like schizophrenia and addiction or cognitive diseases such as Alzheimer’s. Neuromodulatory systems control overlapping cognitive processes and often have similar modes of action; therefore it is important to reveal cooperation and competition between different systems to understand their unique contributions to cognitive functions like learning, memory and attention. This is only possible by direct comparison, which necessitates monitoring multiple neuromodulatory systems under identical experimental conditions. Moreover, simultaneous recording of different neuromodulatory cell types goes beyond phenomenological description of similarities and differences by revealing the underlying correlation structure at the level of action potential timing. However, such data allowing direct comparison of neuromodulatory actions are still sparse. As a first step to bridge this gap, I propose to elucidate the unique versus complementary roles of two “classical” neuromodulatory systems, the cholinergic and dopaminergic projection system implicated in various cognitive functions including associative learning and plasticity. First, we will record optogenetically identified cholinergic and dopaminergic neurons simultaneously using chronic extracellular recording in mice undergoing classical and operant conditioning. Second, we will determine the postsynaptic impact of cholinergic and dopaminergic neurons by manipulating them both separately and simultaneously while recording consequential changes in cortical neuronal activity and learning behaviour. These experiments will reveal how major neuromodulatory systems interact to mediate similar or different aspects of the same cognitive functions.

Neuromodulators such as acetylcholine and dopamine are able to rapidly reprogram neuronal information processing and dynamically change brain states. Degeneration or dysfunction of cholinergic and dopaminergic neurons can lead to neuropsychiatric conditions like schizophrenia and addiction or cognitive diseases such as Alzheimer’s. Neuromodulatory systems control overlapping cognitive processes and often have similar modes of action; therefore it is important to reveal cooperation and competition between different systems to understand their unique contributions to cognitive functions like learning, memory and attention. This is only possible by direct comparison, which necessitates monitoring multiple neuromodulatory systems under identical experimental conditions. Moreover, simultaneous recording of different neuromodulatory cell types goes beyond phenomenological description of similarities and differences by revealing the underlying correlation structure at the level of action potential timing. However, such data allowing direct comparison of neuromodulatory actions are still sparse. As a first step to bridge this gap, I propose to elucidate the unique versus complementary roles of two “classical” neuromodulatory systems, the cholinergic and dopaminergic projection system implicated in various cognitive functions including associative learning and plasticity. First, we will record optogenetically identified cholinergic and dopaminergic neurons simultaneously using chronic extracellular recording in mice undergoing classical and operant conditioning. Second, we will determine the postsynaptic impact of cholinergic and dopaminergic neurons by manipulating them both separately and simultaneously while recording consequential changes in cortical neuronal activity and learning behaviour. These experiments will reveal how major neuromodulatory systems interact to mediate similar or different aspects of the same cognitive functions.

SummaryProper and controlled expression of genes is essential for normal cell growth. Chromatin modifying enzymes play a
fundamental role in the control of gene expression and their deregulation is often linked to cancer. In recent years chromatin
modifiers have been considered key targets for cancer therapy and this demands a full understanding of their biological
functions. Previous biochemical and structural studies have focused on the identification of chromatin modifying enzymes
and characterization of their substrate specificities and catalytic mechanisms. However, a comprehensive view of the
biological processes, signaling pathways and regulatory circuits in which these enzymes participate is missing. Protein
arginine methyltransferases (PRMTs), which methylate histones and are evolutionarily conserved from yeast to human,
constitute an example of chromatin modifying enzymes whose functional and regulatory networks remain unexplored. I
propose to use complementary state-of-the-art genomic and proteomic approaches in order to identify the protein networks
and cellular pathways that are linked to PRMTs. In parallel, I will identify novel regulatory circuits and define the molecular
mechanisms that control methylation of specific histone arginine residues. I will utilize the yeast S. cerevisiae as a model
organism because it allows genetic, biochemical and genomic approaches to be combined. Most importantly, many of the
pathways and mechanisms in yeast are highly conserved and therefore, the findings from this study will be pertinent to
human and other eukaryotic organisms. Establishing a global cellular wiring diagram of PRMTs will serve as a paradigm for
other chromatin modifiers and is imperative for assessing the efficacy of these enzymes as therapeutic targets.

Proper and controlled expression of genes is essential for normal cell growth. Chromatin modifying enzymes play a
fundamental role in the control of gene expression and their deregulation is often linked to cancer. In recent years chromatin
modifiers have been considered key targets for cancer therapy and this demands a full understanding of their biological
functions. Previous biochemical and structural studies have focused on the identification of chromatin modifying enzymes
and characterization of their substrate specificities and catalytic mechanisms. However, a comprehensive view of the
biological processes, signaling pathways and regulatory circuits in which these enzymes participate is missing. Protein
arginine methyltransferases (PRMTs), which methylate histones and are evolutionarily conserved from yeast to human,
constitute an example of chromatin modifying enzymes whose functional and regulatory networks remain unexplored. I
propose to use complementary state-of-the-art genomic and proteomic approaches in order to identify the protein networks
and cellular pathways that are linked to PRMTs. In parallel, I will identify novel regulatory circuits and define the molecular
mechanisms that control methylation of specific histone arginine residues. I will utilize the yeast S. cerevisiae as a model
organism because it allows genetic, biochemical and genomic approaches to be combined. Most importantly, many of the
pathways and mechanisms in yeast are highly conserved and therefore, the findings from this study will be pertinent to
human and other eukaryotic organisms. Establishing a global cellular wiring diagram of PRMTs will serve as a paradigm for
other chromatin modifiers and is imperative for assessing the efficacy of these enzymes as therapeutic targets.

Max ERC Funding

1 498 279 €

Duration

Start date: 2011-01-01, End date: 2016-06-30

Project acronymDeCode

ProjectDendrites and memory: role of dendritic spikes in information coding by hippocampal CA3 pyramidal neurons

SummaryThe hippocampus is essential for building episodic memories. Coding of locations, contexts or events in the hippocampus is based on the correlated activity of neuronal ensembles; however, the mechanisms promoting the recruitment of individual neurons into information-coding ensembles are poorly understood.
In particular, the recurrent synaptic network of pyramidal cells (PCs) in the hippocampal CA3 area, receiving external inputs from the entorhinal cortex and the dentate gyrus, is thought to be essential for associative memory. Current models of the associative functions of CA3 are mainly based on plasticity of these synaptic connections. Recent work by us and others however suggests that active, voltage-dependent properties of CA3PC dendrites may also promote ensemble functions. Dendritic voltage-dependent ion channels allow nonlinear amplification of spatiotemporally correlated synaptic inputs (such as those produced by ensemble activity) and can even generate local dendritic spikes, which may elicit specific action potential patterns and induce synaptic plasticity. Furthermore, dendritic processing may be modulated by activity-dependent regulation of dendritic ion channels. However, still little is known about the active properties of CA3PC dendrites and their functions during spatial coding or memory tasks.
The general aim of my research program is to understand the cellular mechanisms that underlie the formation of hippocampal memory-coding neuronal ensembles. Specifically, we will test the hypothesis that active input integration by dendrites of individual CA3PCs plays an important role in their recruitment into specific context-coding ensembles. By combining in vitro (patch-clamp electrophysiology and two-photon (2P) microscopy in slices) and in vivo (2P imaging and activity-dependent labelling in behaving rodents) approaches, we will provide an in-depth understanding of the dendritic components contributing to the generation of the CA3 ensemble code.

The hippocampus is essential for building episodic memories. Coding of locations, contexts or events in the hippocampus is based on the correlated activity of neuronal ensembles; however, the mechanisms promoting the recruitment of individual neurons into information-coding ensembles are poorly understood.
In particular, the recurrent synaptic network of pyramidal cells (PCs) in the hippocampal CA3 area, receiving external inputs from the entorhinal cortex and the dentate gyrus, is thought to be essential for associative memory. Current models of the associative functions of CA3 are mainly based on plasticity of these synaptic connections. Recent work by us and others however suggests that active, voltage-dependent properties of CA3PC dendrites may also promote ensemble functions. Dendritic voltage-dependent ion channels allow nonlinear amplification of spatiotemporally correlated synaptic inputs (such as those produced by ensemble activity) and can even generate local dendritic spikes, which may elicit specific action potential patterns and induce synaptic plasticity. Furthermore, dendritic processing may be modulated by activity-dependent regulation of dendritic ion channels. However, still little is known about the active properties of CA3PC dendrites and their functions during spatial coding or memory tasks.
The general aim of my research program is to understand the cellular mechanisms that underlie the formation of hippocampal memory-coding neuronal ensembles. Specifically, we will test the hypothesis that active input integration by dendrites of individual CA3PCs plays an important role in their recruitment into specific context-coding ensembles. By combining in vitro (patch-clamp electrophysiology and two-photon (2P) microscopy in slices) and in vivo (2P imaging and activity-dependent labelling in behaving rodents) approaches, we will provide an in-depth understanding of the dendritic components contributing to the generation of the CA3 ensemble code.

Max ERC Funding

1 990 314 €

Duration

Start date: 2018-06-01, End date: 2023-05-31

Project acronymEIRENE

ProjectPost-war trasistions in gendered perspective: the case of the North-Eastern Adricatic Region

Researcher (PI)Marta VERGINELLA

Host Institution (HI)UNIVERZA V LJUBLJANI

Call DetailsAdvanced Grant (AdG), SH6, ERC-2016-ADG

SummaryThe EIRENE project’s purpose is to think afresh 20th-century post-war transitions by taking into account a gendered perspective. Namely, the historiographic consideration of gender thoroughly alters the understanding of social dynamics in multi-ethnic areas during the post-war transitions. They will be observed in the North-Eastern Adriatic region, an overlooked European space, marked by border redefinitions, changes of political systems, and high interethnic conflict intensity, but also by genuine cooperation among ethnic groups. The region has all the qualities of a “laboratory environment” for the study of gender positions and interrelations after World Wars I and II and after the Yugoslav wars in the 1990s. The project will differ substantially from previous attempts to analyse post-war transitions in these aspects: a) longitudinal approach, comparing three post-war periods in order to detect their specifics and (dis)continuities; b) transnational approach, by overcoming nation-centric frameworks of analysis; c) by combining conceptual political and social sciences with historiography; and finally, d) by examining post-war transitions through the prism of gender. Focusing on four research-fields (politics, political violence, work, family), the project will validate innovative analytical concepts of the “inclusion-exclusion paradox” of women in post-war transitions, and women as “cross-boundary mediators”. Within the category of gender, focal attention will be given to women as they are often invisible in historical accounts and remain neglected in historicizing. By aggregating empirical sources, the project will approach the proposed subject matter by investigating the processes of identification across the lines of ethnic origin, class, generations, marital status, profession/occupation, language of use, migratory processes, etc. The project’s added value is its novel conceptual applicability to other comparable geopolitical areas.

The EIRENE project’s purpose is to think afresh 20th-century post-war transitions by taking into account a gendered perspective. Namely, the historiographic consideration of gender thoroughly alters the understanding of social dynamics in multi-ethnic areas during the post-war transitions. They will be observed in the North-Eastern Adriatic region, an overlooked European space, marked by border redefinitions, changes of political systems, and high interethnic conflict intensity, but also by genuine cooperation among ethnic groups. The region has all the qualities of a “laboratory environment” for the study of gender positions and interrelations after World Wars I and II and after the Yugoslav wars in the 1990s. The project will differ substantially from previous attempts to analyse post-war transitions in these aspects: a) longitudinal approach, comparing three post-war periods in order to detect their specifics and (dis)continuities; b) transnational approach, by overcoming nation-centric frameworks of analysis; c) by combining conceptual political and social sciences with historiography; and finally, d) by examining post-war transitions through the prism of gender. Focusing on four research-fields (politics, political violence, work, family), the project will validate innovative analytical concepts of the “inclusion-exclusion paradox” of women in post-war transitions, and women as “cross-boundary mediators”. Within the category of gender, focal attention will be given to women as they are often invisible in historical accounts and remain neglected in historicizing. By aggregating empirical sources, the project will approach the proposed subject matter by investigating the processes of identification across the lines of ethnic origin, class, generations, marital status, profession/occupation, language of use, migratory processes, etc. The project’s added value is its novel conceptual applicability to other comparable geopolitical areas.

Max ERC Funding

2 266 067 €

Duration

Start date: 2017-12-01, End date: 2022-11-30

Project acronymELITES08

ProjectCulturally Composite Elites, Regime Changes and Social Crises in Multi-Ethnic and Multi-Confessional Eastern Europe. (The Carpathian Basin and the Baltics in Comparison - cc. 1900-1950)

Researcher (PI)Gyozo István Karády

Host Institution (HI)KOZEP-EUROPAI EGYETEM

Call DetailsAdvanced Grant (AdG), SH6, ERC-2008-AdG

SummaryThe project is multi-disciplinary by character. It focuses upon socio-historical processes of the transformation and 'circulation' of educated and ruling elites in several uniquely composite (both multi-ethnic and multi-confessional) East European regional or national societies, having experienced a number of radical changes of social and political regime as well as state souvereignty in the first half of the 20th century. The historical scope of the study extends from post-feudalism to communism. Societies involved comprise Hungary, Slovakia, Transylvania, Voivodina in the Carpathian Basin, Latvia and Estonia in the Baltics. The study draws upon sociological survey methods applied to historically successive elite brackets in form of exhaustive or quasi-exhaustive computerized prosopographical data banks, based on standardized individual biographies of elite members (as permitted by mostly archival sources to be exploited). The main targets would include secondary school graduates, students and graduates of higher education, the main intellectual professions (like doctors and lawyers.), the political power elites as well as 'reputational elites' - those cited in biographical dictionaries. The information fed into our data banks help to clarify thanks to various procedures of multi-variate statistical schemes the contrasting socio-cultural selection and recruitment of elite members, their educational path from primary to higher education, their professional career, intellectual creativity as well as socio-political standing and orientation. This is the first time that large region- or country-wide elite clusters are submitted to systematic socio-historical analyses, covering simultaneously all or most markets of activity and self-assertion of educated clusters in a vast international and comparative perspective related to culturally composite societal formations.

The project is multi-disciplinary by character. It focuses upon socio-historical processes of the transformation and 'circulation' of educated and ruling elites in several uniquely composite (both multi-ethnic and multi-confessional) East European regional or national societies, having experienced a number of radical changes of social and political regime as well as state souvereignty in the first half of the 20th century. The historical scope of the study extends from post-feudalism to communism. Societies involved comprise Hungary, Slovakia, Transylvania, Voivodina in the Carpathian Basin, Latvia and Estonia in the Baltics. The study draws upon sociological survey methods applied to historically successive elite brackets in form of exhaustive or quasi-exhaustive computerized prosopographical data banks, based on standardized individual biographies of elite members (as permitted by mostly archival sources to be exploited). The main targets would include secondary school graduates, students and graduates of higher education, the main intellectual professions (like doctors and lawyers.), the political power elites as well as 'reputational elites' - those cited in biographical dictionaries. The information fed into our data banks help to clarify thanks to various procedures of multi-variate statistical schemes the contrasting socio-cultural selection and recruitment of elite members, their educational path from primary to higher education, their professional career, intellectual creativity as well as socio-political standing and orientation. This is the first time that large region- or country-wide elite clusters are submitted to systematic socio-historical analyses, covering simultaneously all or most markets of activity and self-assertion of educated clusters in a vast international and comparative perspective related to culturally composite societal formations.